Upregulation of intracellular glutathione by fibroblast-derived factor(s): Enhanced survival of activated T cells in the presence of low Bcl-2
Upregulation of intracellular glutathione by fibroblast-derived factor(s): Enhanced survival of activated T cells in the presence of low Bcl-2
复制标题
DOI：
10.1182/blood.v89.7.2453
复制
发表时间：
1997-04-01
期刊：
影响因子：
20.3
通讯作者：
Akbar, AN
中科院分区：
文献类型：
--
作者：
Hyde, H;Borthwick, NJ;Akbar, AN
激活的白细胞介素-2 （IL-2）依赖的T细胞表达高水平的Bcl-2蛋白，当细胞因子停用时，Bcl-2表达降低，细胞凋亡迅速死亡。我们之前已经证明，il -2缺失的T细胞的存活可以通过成纤维细胞分泌的因子来促进，这里我们报道还原型谷胱甘肽（GSH），而不是其氧化对偶物CSSG，也可以提高这些细胞的体外存活。外源性谷胱甘肽介导其在细胞内的作用，因为(1)内源性谷胱甘肽浓度在谷胱甘肽存在时增加了5倍，(2)acvicin，一种跨膜谷胱甘肽运输抑制剂，消除了谷胱甘肽依赖的存活。谷胱甘肽拯救的T细胞不增殖，只表达低水平的Bcl-2，类似于W138成纤维细胞拯救的T细胞。因此，我们研究了谷胱甘肽在成纤维细胞促进的T细胞存活中的作用。我们发现w138促进存活导致存活T细胞中GSH水平升高，并被一种GSH合成抑制剂——丁硫氨酸亚砜胺（BSO）所消除。此外，w138促进的t细胞存活和GSH上调都与大分子量分子（>30 kD）有关。因此，W138成纤维细胞对谷胱甘肽的上调似乎是提高体外细胞因子剥夺激活T细胞存活率的关键。(C) 1997年由美国血液病学会出版。
Activated interleukin-2 (IL-2)-dependent T cells express high levels of Bcl-2 protein, On cytokine withdrawal, Bcl-2 expression decreases and the cells die rapidly by apoptosis. We have previously shown that the survival of IL-2-deprived T cells can be promoted by factor(s) secreted by fibroblasts, Here we report that reduced glutathione (GSH), but not its oxidized counterpart CSSG, also enhances the in vitro survival of these cells. Exogenous GSH mediates its effect intracellularly, as (1) endogenous glutathione concentrations are increased up to fivefold in the presence of GSH, and (2) acivicin, an inhibitor of transmembrane GSH transport, abrogates GSH-dependent survival, The GSH-rescued T cells do not proliferate and express only low levels of Bcl-2, resembling W138 fibroblast-rescued T cells, We, therefore, investigated a role for GSH in fibroblast-promoted T-cell survival. We show that W138-promoted survival results in elevated GSH levels in surviving T cells and is abrogated by buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. Furthermore, both W138-promoted T-cell survival and GSH upregulation are associated with large molecular weight molecules (>30 kD). Thus, the upregulation of GSH by W138 fibroblasts appears to be crucial in their ability to enhance the survival of cytokine-deprived activated T cells in vitro. (C) 1997 by The American Society of Hematology.